<![CDATA[Sertraline (BCS class II) has low solubility and dissolution rate. Modifying sertraline through multicomponent crystal formation is a strategy to enhance its physicochemical properties, particularly solubility and dissolution. This study aimed to design, formulate, and characterize sertraline tablets based on multicomponent crystals using L-tryptophan (S–L), saccharin (S–S), and nicotinic acid (S–N) as coformers. The crystals were synthesized by solvent evaporation and characterized using FTIR, DSC, PXRD, SEM, and solubility and dissolution studies, followed by evaluation of tablet properties using direct compression. The multicomponent crystals exhibited FTIR band shifts or broadening of –OH/–NH and C=O groups and new PXRD peaks, indicating the formation of multicomponent crystals. DSC showed distinct thermal transitions: S–L at 258 °C, S–S at 280.8 °C, and S–N at 242 °C. The highest solubility enhancement was observed for S–N (44.29 mg/10 mL, followed by S–L (15.44 mg/10 mL). In 0.1 N HCl medium, 60-minute dissolution reached >88% for S–N, 73% for S–L, 53% for S–S, and 52% for pure sertraline. The best tablet formulation (F6) demonstrated good flow and compressibility (compressibility index 23.55%, angle of repose 28.85°, flow rate 6.53 g/s) and met pharmacopeial criteria: uniform dimensions (8 mm diameter, 5.23 mm thickness), weight (284.22 mg), (friability (0.37%), hardness (6.66 kg/cm2), disintegration (5.47 seconds), and dissolution at pH 4.5 ≥85% in 30 minutes. Multicomponent crystals of sertraline-nicotinic acid are able to increase solubility up to 8.8 fold and can be produced by direct compression method and produce good evaluation of tablet preparations (uniformity of weight, friability, hardness, disintegration time test, and dissolution test) in immediate release tablet formulation.]]>
